Continuous Glucose Monitoring Metrics for Pregnancies Complicated by Diabetes: Critical Appraisal of Current Evidence.

Ascertaining the utility of continuous glucose monitoring (CGM) in pregnancy complicated by diabetes is a rapidly evolving area, as the prevalence of type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) escalates. The seminal randomized controlled trial (RCT) evaluating CGM use added to standard care in pregnancy in T1D demonstrated significant improvements in maternal glycemia and neonatal health outcomes. Current clinical guidance recommends targets for percentage time in range (TIR), time above range (TAR), and time below range (TBR) during pregnancy complicated by T1D that are widely used in clinical practice. However, the superiority of CGM over blood glucose monitoring (BGM) is still questioned in both T2D and GDM, and whether glucose targets should be different than in T1D is unknown. Questions requiring additional research include which CGM metrics are superior in predicting clinical outcomes, how should pregnancy-specific CGM targets be defined, whether CGM targets should differ according to gestational age, and if CGM metrics during pregnancy should be similar across all types of diabetes. Limiting the potential for CGM to improve pregnancy outcomes may be our inability to maintain TIR > 70% throughout gestation, a goal achieved in the minority of patients studied. Adverse pregnancy outcomes remain high in women with T1D and T2D in pregnancy despite CGM technology, and this review explores the potential reasons and questions yet to be investigated.

Beyond A1C: exploring continuous glucose monitoring metrics in managing diabetes.

Hemoglobin A1c (HbA1c) has long been considered a cornerstone of diabetes mellitus (DM) management, as both an indicator of average glycemia and a predictor of long-term complications among people with DM. However, HbA1c is subject to non-glycemic influences which confound interpretation and as a measure of average glycemia does not provide information regarding glucose trends or about the occurrence of hypoglycemia and/or hyperglycemia episodes. As such, solitary use of HbA1c, without accompanying glucose data, does not confer actionable information that can be harnessed to guide targeted therapy in many patients with DM. While conventional capillary blood glucose monitoring (BGM) sheds light on momentary glucose levels, in practical use the inherent infrequency of measurement precludes elucidation of glycemic trends or reliable detection of hypoglycemia or hyperglycemia episodes. In contrast, continuous glucose monitoring (CGM) data reveal glucose trends and potentially undetected hypo- and hyperglycemia patterns that can occur between discrete BGM measurements. The use of CGM has grown significantly over the past decades as an ever-expanding body of literature demonstrates a multitude of clinical benefits for people with DM. Continually improving CGM accuracy and ease of use have further fueled the widespread adoption of CGM. Furthermore, percent time in range correlates well with HbA1c, is accepted as a validated indicator of glycemia, and is associated with the risk of several DM complications. We explore the benefits and limitations of CGM use, the use of CGM in clinical practice, and the application of CGM to advanced diabetes technologies.

Use of Continuous Glucose Monitors to Manage Type 1 Diabetes Mellitus: Progress, Challenges, and Recommendations.

Type 1 diabetes (T1D) management has been revolutionized with the development and routine utilization of continuous glucose monitoring (CGM). CGM technology has allowed for the ability to track dynamic glycemic fluctuations and trends over time allowing for optimization of medical therapy and the prevention of dangerous hypoglycemic events. This review details currently-available real-time and intermittently-scanned CGM devices, clinical benefits, and challenges of CGM use, and current guidelines supporting its use in the clinical care of patients with T1D. We additionally describe future issues that will need to be addressed as CGM technology continues to evolve.

Expert Guidance on Off-Label Use of Hybrid Closed-Loop Therapy in Pregnancies Complicated by Diabetes.

Automated insulin delivery (AID) systems have established benefits in terms of glycemic control, health outcomes, and quality of life and are strongly recommended for people with type 1 diabetes outside of pregnancy. While evidence for use of investigational AID systems during pregnancy is promising, data and guidance are still needed regarding use of commercially available systems during pregnancy. Unfortunately, none of the hybrid closed-loop (HCL) systems that are currently available in the United States have glucose targets that are as aggressive as pregnancy glycemic targets, none have a pregnancy-specific algorithm, and none are approved for use during pregnancy. As such, any use of these systems during pregnancy is considered off-label in the United States and would be "assisted" by provider/user techniques. Despite these limitations, many women conceive while using clinically available HCL systems and may be hesitant to cease use during pregnancy. Achievement of strict pregnancy glycemic targets can be difficult, and it is conceivable that selective off-label use of clinically available HCL systems in some women could lead to improved glycemia. We herein offer expert guidance based on clinical experience and available case reports on how to identify appropriate candidates for HCL therapy in pregnancy, how to counsel pregnant women with diabetes on the potential risks and benefits of HCL therapy during pregnancy, and how to manage commercially available systems off-label throughout gestation in an assisted HCL approach.

Stepwise approach to continuous glucose monitoring interpretation for internists and family physicians.

Continuous glucose monitoring (CGM) use has expanded rapidly in recent years among people with both type 1 and type 2 diabetes. In concert with the globally increasing prevalence of type 2 diabetes, the majority of whom receive diabetes care from internists or family physicians rather than specialists, it is becoming increasingly incumbent upon physicians within internal medicine and family practice to interpret and utilize CGM data in real-world clinical practice. It is therefore of paramount importance that internists and family physicians have access to the tools which will enable them to (1) interpret CGM data, and (2) utilize CGM data to guide therapeutic modifications for their patients with type 2 diabetes. Given the limited amount of time available to internists and family physicians to address multiple complex topics in a typical office visit, a pragmatic, simple, and systematic approach to CGM interpretation is crucial. This article aims to provide internists and family physicians with a simplified and systematic approach to CGM interpretation that can be easily and efficiently implemented in a brief office visit.

Continuous glucose monitoring (CGM) allows people with diabetes to automatically monitor glucose levels throughout the day and night, helps them to make informed decisions about food choices and physical activity, and assists people with diabetes and their healthcare providers in adjusting diabetes medications. CGM use has increased greatly in recent years among people with both type 1 and type 2 diabetes. As the number of people with type 2 diabetes increases around the world, internists and family physicians increasingly need to understand CGM data and guide their patients who use CGM. As a result, internists and family physicians need to have the tools which will enable them to (1) interpret CGM data, and (2) use CGM data to help their patients adjust their diabetes therapies. Since internists and family physicians have limited time to address many medical issues in a typical office visit, a simple and systematic approach to CGM interpretation is needed. This article aims to provide internists and family physicians with a simple and orderly approach to CGM interpretation that can be easily and efficiently used in a brief office visit.

An Assessment of Diversity, Inclusion, and Health Equity Training in Endocrinology Fellowship Programs in the United States.

CONTEXT: The Accreditation Council for Graduate Medical Education has instituted common program requirements related to diversity, equity, and inclusion (DEI) for postgraduate trainees in the United States; however, the extent to which DEI training is being incorporated across endocrinology fellowship programs is unknown. OBJECTIVES: To describe the sociodemographic representation and DEI training experiences within endocrinology fellowship programs. DESIGN, SETTING, AND PARTICIPANTS: National cross-sectional survey study of fellows and fellowship program leaders in the United States whose fellowships were members of the Association of Program Directors in Endocrinology and Metabolism. MAIN OUTCOME MEASURES: (1) Demographics of fellows and program leaders and (2) programs' experience, confidence, and interest in formal DEI training. RESULTS: A total of 108 and 106 fellow and faculty responded to the survey, respectively. The majority of fellows and faculty are female. Less than 3% of fellows and 3.7% of faculty identify as Black. More than 90% of fellows/faculty are heterosexual and no respondents identified as transgender/nonbinary; however, 5% and 2% of all respondents preferred not to disclose their sexual orientation and gender identity, respectively. While 85% of faculty received institutional diversity and inclusion training, 67.6% of fellows did. Fellows are more likely to have received training in health equity than program leaders. Both fellows and program leaders express a high interest in health equity curriculum. CONCLUSIONS: Within the diversity of endocrinology training programs, Black physicians are underrepresented in medicine, which persists in endocrinology fellowships. Fellowship programs express enthusiasm for national diversity and health equity curricula, with the majority of programs reporting institutional DEI training.

Combination Use of U-500 Regular Insulin via Insulin Pump and Rapid-Acting U-100 Prandial Injections for Treatment of Pre-Existing Type 2 Diabetes in Pregnancy.

The high-dose large-volume insulin injections that may become necessary during pregnancy due to marked pregnancy-induced insulin resistance may result in suboptimal therapeutic effectiveness. Use of U-500 insulin, a concentrated insulin formulation, has been suggested during pregnancy. However, the pharmacokinetic properties of U-500 insulin monotherapy can impede achievement of strict pregnancy glycemic targets. We propose a novel regimen for treatment of severe pregnancy-induced insulin resistance that enables precise delivery of U-500 basal insulin therapy through continuous subcutaneous insulin infusion (CSII) while maintaining the desired kinetics of prandial rapid-acting U-100 insulin therapy. This combination approach, guided by continuous glucose monitoring data, enabled achievement of pregnancy glycemic targets while reducing basal insulin requirements by approximately one-third. We report our method for (1) conversion to U-500 insulin delivery through CSII during pregnancy and (2) conversion from U-500 basal insulin delivery through CSII to U-100 intravenous insulin infusion therapy at delivery, to offer clinicians who encounter similar challenging scenarios a novel approach to diabetes management during pregnancy in the setting of marked insulin resistance.

Gestational Diabetes Mellitus.

Although it has been accepted for decades that women with gestational diabetes mellitus (GDM) are at high risk for future development of type 2 diabetes, vigorous debate regarding the value of detecting and treating GDM has persisted into the twenty-first century. Although results from 2 randomized trials provide strong evidence that treating GDM reduces adverse perinatal outcomes, it remains to be determined whether treatment impacts long-term offspring outcomes. Insulin is the first-line pharmacologic treatment and is added when glycemic goals are not met with nutritional modifications. Oral agent use is controversial, as data on long-term offspring outcomes are lacking.

Management of Diabetes in the Intrapartum and Postpartum Patient.

Achieving maternal euglycemia in women with pregestational and gestational diabetes mellitus is critical to decreasing the risk of neonatal hypoglycemia, as maternal blood glucose levels around the time of delivery are directly related to the risk of hypoglycemia in the neonate. Many institutions use continuous insulin and glucose infusions during the intrapartum period, although practices are widely variable. At Northwestern Memorial Hospital, the "Management of the Perinatal Patient with Diabetes" policy and protocol was developed to improve consistency of management while also allowing individualization appropriate for the patient's specific diabetic needs. This protocol introduced standardized algorithms based on maternal insulin requirements to drive real-time maternal glucose control during labor as well as provided guidelines for postpartum glycemic control. This manuscript describes the development and implementation of this protocol to encourage other institutions to adopt a standardized protocol that allows highly individualized intrapartum care to women with diabetes.

CENTRAL DIABETES INSIPIDUS AND CHEMOTHERAPY: USE OF A CONTINUOUS ARGININE VASOPRESSIN INFUSION FOR FLUID AND SODIUM BALANCE.

OBJECTIVE: Central diabetes insipidus can occur in the setting of primary or metastatic tumors that disrupt the hypothalamic-pituitary axis. Usual treatment consists of water intake to replace ongoing fluid losses and desmopressin administration aimed at decreasing the urine output to enable maintenance of eunatremia without polyuria. Marked derangement in plasma sodium concentration can occur when high-volume intravenous fluid administration is required during chemotherapy to prevent nephrotoxicity, particularly if obligate fluid intake exceeds the total daily fluid intake necessary to maintain eunatremia. METHODS: We developed a protocol for a rapidly titratable low-dose continuous intravenous arginine vasopressin infusion to maintain eunatremia in patients with central diabetes insipidus during periods of obligate fluid intake. RESULTS: We successfully maintained eunatremia in 2 patients with central nervous system lymphoma who underwent several cycles of obligate intravenous fluid administration with 5% dextrose in 0.45% sodium chloride for chemotherapy. CONCLUSION: Obligate fluid administration can result in dangerous and severe fluctuations in plasma sodium concentration in patients with central diabetes insipidus receiving conventional desmopressin therapy. The use of a rapidly titratable low-dose continuous vasopressin infusion successfully maintained eunatremia in this setting. This protocol can be replicated to prevent the wide and potentially dangerous fluctuations in plasma sodium concentration that can occur in patients with central diabetes insipidus who require high-volume intravenous fluid administration. This protocol has not been assessed among patients with impaired renal function and, thus, may not be generalizable to this population. (AACE Clinical Case Rep. 2018;4:e487-e492).

Vasomotor symptoms and cardiovascular events in postmenopausal women.

OBJECTIVE: Emerging evidence suggests that women with menopausal vasomotor symptoms (VMS) have increased cardiovascular disease (CVD) risk as measured by surrogate markers. We investigated the relationships between VMS and clinical CVD events and all-cause mortality in the Women's Health Initiative Observational Study (WHI-OS). METHODS: We compared the risk of incident CVD events and all-cause mortality between four groups of women (total N = 60,027): (1) no VMS at menopause onset and no VMS at WHI-OS enrollment (no VMS [referent group]), (2) VMS at menopause onset but not at WHI-OS enrollment (early VMS), (3) VMS at both menopause onset and WHI-OS enrollment (persistent VMS [early and late]), and (4) VMS at WHI-OS enrollment but not at menopause onset (late VMS). RESULTS: For women with early VMS (n = 24,753), compared with no VMS (n = 18,799), hazard ratios (95% CIs) in fully adjusted models were as follows: major coronary heart disease (CHD), 0.94 (0.84-1.06); stroke, 0.83 (0.72-0.96); total CVD, 0.89 (0.81-0.97); and all-cause mortality, 0.92 (0.85-0.99). For women with persistent VMS (n = 15,084), there was no significant association with clinical events. For women with late VMS (n = 1,391), compared with no VMS, hazard ratios (95% CIs) were as follows: major CHD, 1.32 (1.01-1.71); stroke, 1.14 (0.82-1.59); total CVD, 1.23 (1.00-1.52); and all-cause mortality, 1.29 (1.08-1.54). CONCLUSIONS: Early VMS were not associated with increased CVD risk. Rather, early VMS were associated with decreased risk of stroke, total CVD events, and all-cause mortality. Late VMS were associated with increased CHD risk and all-cause mortality. The predictive value of VMS for clinical CVD events may vary with the onset of VMS at different stages of menopause. Further research examining the mechanisms underlying these associations is needed. Future studies will also be necessary to investigate whether VMS that develop for the first time in the later postmenopausal years represent a pathophysiologic process distinct from the classic perimenopausal VMS.

Influence of menopause on diabetes and diabetes risk.

Many postmenopausal women live with diabetes mellitus; however, little information is available about how the changes that occur around the time of menopause might uniquely affect management of diabetes mellitus in this population. Although the weight gain that commonly occurs during the menopausal transition is largely attributable to aging rather than the transition itself, changes in body composition have been independently associated with menopausal status. These changes in body composition have, in turn, been associated with alterations in insulin sensitivity and glucose metabolism in postmenopausal women. Hormone therapy seems to have neutral or beneficial effects on the adverse changes in body composition associated with menopause. Whether menopausal status independently influences diabetes risk remains controversial. Nevertheless, consistent findings from large clinical trials suggest that postmenopausal hormone therapy decreases the risk of developing diabetes mellitus. Similarly, many studies suggest that postmenopausal hormone therapy has neutral or beneficial effects on glycemic control among women already diagnosed as having diabetes mellitus. Future studies are needed to elucidate the mechanisms that underlie these relationships and to determine how these observations should influence recommendations for the care of postmenopausal women with diabetes mellitus.

HIV/AIDS: AIDS Drug Assistance Programs in the era of routine HIV testing.

AIDS [Acquired Immunodeficiency Syndrome] Drug Assistance Programs, operating within the larger Ryan White Program, are state-based, discretionary programs that provide a drug "safety net" for low-income and uninsured individuals infected with human immunodeficiency virus (HIV). Although the AIDS Drug Assistance Programs and the primary care system that provides care for patients with HIV infection are already financially stressed, the Centers for Disease Control and Prevention recently issued guidelines recommending universal HIV testing to help identify the estimated 300,000 individuals in the United States who are unaware that they are infected with HIV. As the number of people living with HIV/AIDS who are coinfected with hepatitis C virus has grown and the cost and complexity of care have increased, the sustainability of the current HIV care system requires a reevaluation in light of the new testing guidelines. We examine the current state of the AIDS Drug Assistance Programs, discuss the implications of the Centers for Disease Control and Prevention guidelines for the already overstretched Ryan White Program, and consider a federally supported national program to ensure high-quality, efficient HIV care for low-income HIV-infected Americans.

Relationships between endogenous sex hormone concentrations and vascular function in postmenopausal women.

CONTEXT: Differences in postmenopausal endogenous sex hormone concentrations are associated with varying risks of a growing number of common diseases. The relationships between postmenopausal endogenous sex hormone concentrations and vascular function are not well understood. OBJECTIVE: We examined in postmenopausal women the relationships between endogenous sex hormone concentrations and both blood pressure (BP) and renal vascular resistance (RVR), at baseline and in response to infused angiotensin II (AngII). SUBJECTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A total of 34 hypertensive, postmenopausal women were studied in low-sodium and/or high-sodium balance. Serum estradiol, serum progesterone, BP, and RVR were measured at baseline. BP and RVR were remeasured after AngII infusion. RESULTS: In low-sodium balance, the increases in systolic and diastolic BP in response to infused AngII were blunted with increased serum progesterone concentrations (P < 0.05). The increase in RVR in response to infused AngII was also blunted with increased serum progesterone concentrations (P < 0.005). The relationships between progesterone concentration and vascular response to AngII were independent of age, body mass index, and estradiol concentration. There were no significant correlations between estradiol concentration and BP or RVR response to AngII. There were no significant correlations between sex hormone concentrations and baseline BP or RVR. In high-sodium balance, there were no significant associations between sex hormone concentrations and vascular measures. CONCLUSIONS: In postmenopausal women in low-sodium balance, the pressor and renovascular responses to AngII are blunted with increased endogenous progesterone concentrations. Our findings suggest a role for endogenous progesterone in modulating vascular function, even within the low postmenopausal range.